First-site-metastasis pattern in patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with or without immune check-point inhibition: a retrospective analysis

Kerstin Hofstetter; Julian Taugner; Lukas Käsmann; Sina Mansoorian; Benedikt Flörsch; Chukwuka Eze; Amanda Tufman; Niels Reinmuth; Thomas Duell; Claus Belka; Farkhad Manapov

doi:10.1007/s00066-023-02175-6

First-site-metastasis pattern in patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with or without immune check-point inhibition: a retrospective analysis

Strahlenther Onkol. 2023 Nov 17. doi: 10.1007/s00066-023-02175-6. Online ahead of print.

Authors

Kerstin Hofstetter¹, Julian Taugner², Lukas Käsmann^{1

3

4}, Sina Mansoorian¹, Benedikt Flörsch¹, Chukwuka Eze¹, Amanda Tufman^{3

5}, Niels Reinmuth⁶, Thomas Duell⁶, Claus Belka^{1

3

4}, Farkhad Manapov^{1

3

4}

Affiliations

¹ Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
² Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany. Julian.Taugner@med.uni-muenchen.de.
³ Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany.
⁴ German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
⁵ Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich, LMU Munich, Munich, Germany.
⁶ Asklepios Kliniken GmbH, Asklepios Fachkliniken Muenchen, Gauting, Germany.

PMID: 37975883
DOI: 10.1007/s00066-023-02175-6

Abstract

Purpose: The aim of this study was to investigate a first-site-metastasis pattern (FSMP) in unresectable stage III NSCLC after concurrent chemoradiotherapy (cCRT) with or without immune checkpoint inhibition (ICI).

Methods: We defined three patient subgroups according to the year of initial multimodal treatment: A (2011-2014), B (2015-2017) and C (2018-2020). Different treatment-related parameters were analyzed. Observed outcome parameters were brain metastasis-free survival (BMFS), extracranial distant metastasis-free survival (ecDMFS) and distant metastasis-free survival (DMFS).

Results: 136 patients treated between 2011 and 2020 were included with ≥ 60.0 Gy total dose and concurrent chemotherapy (cCRT); thirty-six (26%) received ICI. Median follow-up was 49.7 (range:0.7-126.1), median OS 31.2 (95% CI:16.4-30.3) months (23.4 for non-ICI vs not reached for ICI patients, p = 0.001). Median BMFS/ecDMFS/DMFS in subgroups A, B and C was 14.9/16.3/14.7 months, 20.6/12.9/12.7 months and not reached (NR)/NR/36.4 months (p = 0.004/0.001/0.016). For cCRT+ICI median BMFS was 53.1 vs. 19.1 months for cCRT alone (p = 0.005). Median ecDMFS achieved 55.2 vs. 17.9 (p = 0.003) and median DMFS 29.5 (95% CI: 1.4-57.6) vs 14.93 (95% CI:10.8-19.0) months (p = 0.031), respectively. Multivariate analysis showed that age over 65 (HR:1.629; p = 0.036), GTV ≥ 78 cc (HR: 2.100; p = 0.002) and V20 ≥ 30 (HR: 2.400; p = 0.002) were negative prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS (HR: 1.739; p = 0.027). After onset of brain metastasis (BM), patients survived 13.3 (95% CI: 6.4-20.2) months and 8.6 months (95% CI: 1.6-15.5) after extracranial-distant-metastasis (ecDM). Patients with ecDM as FSMP reached significantly worse overall survival of 22.1 (range:14.4-29.8) vs. 40.1 (range:18.7-61.3) months (p = 0.034) in the rest of cohort. In contrast, BM as FSMP had no impact on OS.

Conclusion: This retrospective analysis of inoperable stage III NSCLC patients revealed that age over 65, V20 ≥ 30 and GTV ≥ 78 cc were prognosticators for BMFS and GTV ≥ 78 cc for ecDMFS. ICI treatment led to a significant improvement of BMFS, ecDMFS and DMFS. ecDM as FSMP was associated with significant deterioration of OS, whereas BM as FSMP was not.

Keywords: Immune Checkpoint Inhibition; Lung Cancer; Metastasis; Outcome; Thoracic Radiotherapy.